Optically pure (+)-colchicine binds substantially less to tublin in vitro than the natural alkaloid. An efficient conversion of colchicine into demecolcine has been accomplished. Three phenolic colchicine analogs have been characterized by physical measurements. The X-ray structure of a colchiceine hydrate has been obtained, showing that it is the keto enol of colchicine. It has been further substantiated that the N-acetamido group of colchicine is not necessary for tubulin binding. Compounds showing good binding to tubulin have been evaluated toxicologically and promising, less toxic compounds, have been submitted to NCI for in vivo evaluation. Speciosine, a rare alkaloid from Colchicum autumnale, is substantially less toxic than colchicine.